Androgen receptor-induced lncRNA SOX2-OT promotes triple-negative breast cancer tumorigenesis via targeting miR-320a-5p-CCR5 axis.

Abstract

Our previous study showed that androgen receptor (AR) promotes triple-negative breast cancer (TNBC) cell tumorigenesis, but the underlying mechanisms remain unclear. Herein, using microarray analysis of long noncoding RNA expression profiles, we identified an AR-related long noncoding RNA SOX2-OT in TNBC. We found that AR could promote TNBC tumorigenesis by acting as a transcription factor to activate the expression of SOX2-OT. Mechanistic analysis demonstrated that SOX2-OT serves as a molecular sponge for miR-320a-5p to regulate the expression of CCR5. In addition, SOX2-OT promotes TNBC cell proliferation and inhibits apoptosis in an miR-320a-5p-dependent manner. Using a xenograft mouse model, we found that SOX2-OT-CCR5 axis could promote TNBC tumorigenesis in vivo. Importantly, the AR-SOX2-OT-miR-320a-5p-CCR5 axis is manifested in the tissues of 165 TNBC patients. Collectively, our results suggest that SOX2-OT can regulate AR-induced TNBC tumorigenesis through the miR-320a-5p-CCR5 signaling axis and reveal the great potential of targeting SOX2-OT for the treatment of TNBC patients.